Case report - Hair shaft normalization and hair growth in SPINK5-syndromic epidermal differentiation disorder (Netherton syndrome) while on treatment with dupilumab: a novel therapeutic approach for Trichorrhexis invaginata

Introduction SPINK5-syndromic epidermal differentiation disorder (also known as Netherton syndrome (NS)) is a severe chronic genetic disorder characterized by skin inflammation, severe atopy and Trichorrhexis invaginata (TI). Causative SPINK5 gene mutations result in defective serin protease inhibitor LEKTI, leading to unopposed serine protease activity and resulting in impaired skin barrier and type 2 inflammation. TI is the result of an intermittent keratinization defect of the hair cortex, a problem without specific treatment available to date. Case Presentation We diagnosed NS in a 67-year-old woman who had severe skin manifestations and a hair-growth defect since childhood. Scalp hair was sparse in the nuchal and temporoparietal regions. Trichoscopy of these areas showed numerous “bamboo” hairs which broke off during contact with the dermatoscope. We initiated treatment with dupilumab and optimized the topical therapy. At a 3-month follow-up, improvement of rash, pruritus and quality of life was reported. Furthermore, the previously brittle short hair was replaced with longer hair, and normal hair shafts in the previously affected areas. Conclusion Trichorrhexis invaginata as part of Netherton syndrome has a variable presentation, biologics currently treating cutaneous inflammation, but little is known about their effects on hair biology. In this report we show that Dupilumab treatment not only proved efficient for control of skin inflammation and pruritus, but was associated with near complete resolution of “bamboo” hair and promoted hair growth. Especially how alterations in the inflammatory response in NS can be linked to a structural defect has not been addressed in the current literature so far.